PMID- 35143305 OWN - NLM STAT- MEDLINE DCOM- 20220218 LR - 20230314 IS - 1095-9203 (Electronic) IS - 0036-8075 (Print) IS - 0036-8075 (Linking) VI - 375 IP - 6581 DP - 2022 Feb 11 TI - CD97 promotes spleen dendritic cell homeostasis through the mechanosensing of red blood cells. PG - eabi5965 LID - 10.1126/science.abi5965 [doi] AB - Dendritic cells (DCs) are crucial for initiating adaptive immune responses. However, the factors that control DC positioning and homeostasis are incompletely understood. We found that type-2 conventional DCs (cDC2s) in the spleen depend on Galpha(13) and adhesion G protein-coupled receptor family member-E5 (Adgre5, or CD97) for positioning in blood-exposed locations. CD97 function required its autoproteolytic cleavage. CD55 is a CD97 ligand, and cDC2 interaction with CD55-expressing red blood cells (RBCs) under shear stress conditions caused extraction of the regulatory CD97 N-terminal fragment. Deficiency in CD55-CD97 signaling led to loss of splenic cDC2s into the circulation and defective lymphocyte responses to blood-borne antigens. Thus, CD97 mechanosensing of RBCs establishes a migration and gene expression program that optimizes the antigen capture and presentation functions of splenic cDC2s. FAU - Liu, Dan AU - Liu D AUID- ORCID: 0000-0002-5601-8053 AD - Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA. AD - Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Duan, Lihui AU - Duan L AD - Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA. AD - Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Rodda, Lauren B AU - Rodda LB AUID- ORCID: 0000-0001-7763-8166 AD - Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA. AD - Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Lu, Erick AU - Lu E AUID- ORCID: 0000-0001-8175-5146 AD - Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA. AD - Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Xu, Ying AU - Xu Y AD - Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA. AD - Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - An, Jinping AU - An J AD - Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA. AD - Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Qiu, Longhui AU - Qiu L AD - Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Liu, Fengchun AU - Liu F AUID- ORCID: 0000-0003-0775-0608 AD - Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Looney, Mark R AU - Looney MR AUID- ORCID: 0000-0003-0241-9190 AD - Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Yang, Zhiyong AU - Yang Z AUID- ORCID: 0000-0003-0589-6224 AD - Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143, USA. AD - Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA. AD - Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Allen, Christopher D C AU - Allen CDC AUID- ORCID: 0000-0002-1879-9047 AD - Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143, USA. AD - Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA. AD - Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Li, Zhongmei AU - Li Z AD - J. David Gladstone Institutes, San Francisco, CA 94158, USA. FAU - Marson, Alexander AU - Marson A AUID- ORCID: 0000-0002-2734-5776 AD - Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA. AD - Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. AD - J. David Gladstone Institutes, San Francisco, CA 94158, USA. FAU - Cyster, Jason G AU - Cyster JG AUID- ORCID: 0000-0002-4735-9745 AD - Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA. AD - Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA. LA - eng GR - R01 AI040098/AI/NIAID NIH HHS/United States GR - R37 AI040098/AI/NIAID NIH HHS/United States GR - T32 AI007334/AI/NIAID NIH HHS/United States GR - HHMI/Howard Hughes Medical Institute/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20220211 PL - United States TA - Science JT - Science (New York, N.Y.) JID - 0404511 RN - 0 (Actins) RN - 0 (Adgre5 protein, mouse) RN - 0 (Antigens) RN - 0 (CD55 Antigens) RN - 0 (Interferon Regulatory Factors) RN - 0 (Ligands) RN - 0 (Receptors, G-Protein-Coupled) RN - 0 (interferon regulatory factor-4) RN - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, G12-G13) SB - IM MH - Actins/metabolism MH - Animals MH - Antigen Presentation MH - Antigens/immunology MH - Blood Circulation MH - CD55 Antigens/blood/metabolism MH - Cell Movement MH - Dendritic Cells/immunology/*physiology MH - Erythrocytes/metabolism/*physiology MH - GTP-Binding Protein alpha Subunits, G12-G13/metabolism MH - Homeostasis MH - Interferon Regulatory Factors/metabolism MH - Ligands MH - Mice MH - Receptors, G-Protein-Coupled/genetics/*metabolism MH - Signal Transduction MH - Spleen/blood supply/*cytology/*immunology/metabolism MH - Transcription, Genetic MH - Transcriptome PMC - PMC9310086 MID - NIHMS1822926 EDAT- 2022/02/11 06:00 MHDA- 2022/02/19 06:00 PMCR- 2023/02/11 CRDT- 2022/02/10 17:14 PHST- 2022/02/10 17:14 [entrez] PHST- 2022/02/11 06:00 [pubmed] PHST- 2022/02/19 06:00 [medline] PHST- 2023/02/11 00:00 [pmc-release] AID - 10.1126/science.abi5965 [doi] PST - ppublish SO - Science. 2022 Feb 11;375(6581):eabi5965. doi: 10.1126/science.abi5965. Epub 2022 Feb 11.